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Cyclic AMP in pancreatic and biliary secretion of children with chronic intrahepatic cholestasis and cystic fibrosis

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Abstract

The intracellular transmitter cAMP enters the extracellular space and can be found in the duodenal fluid. The role of this messenger was investigated in response to secretin and CCK in children with secretory insufficiency, i.e. 7 with chronic intrahepatic cholestasis, 7 with cystic fibrosis, and 6 controls.

Duodenal juice was collected in 10 min aliquots before and after stimulation with 2 U/kg secretin and subsequently 2 U/kg CCK. cAMP, bicarbonate, Ca++, Na+, K+, bilirubin, protein, amylase, trypsin and lipase were determined.

Controls. After the injection of secretin the cAMP concentration increased 2.5-fold, the output 6-fold. Compared to cAMP, the time-concentration curve of bicarbonate and Na+, as well as volume output, were slightly delayed after secretin, whereas Ca++ and bilirubin concentrations decreased. CCK stimulation resulted in an increase of volume, bicarbonate-Na+, Ca++-, bilirubin-, protein- and hydrolase concentration. cAMP concentration increased 1.7-fold and the output was doubled.

Chronic Intrahepatic Cholestasis. Following secretin the cAMP concentration hardly differed from the control values; the output of cAMP, bicarbonate and Na+ was enhanced. Compared to the controls CCK was less effective—the concentration and output of cAMP, bilirubin, K+ and Ca++ were diminished.

Cystic Fibrosis. After both hormones high concentrations of cAMP, Na+, K+, Ca++ and bilirubin were found. Due to the reduced secretion volume the output of these parameters were significantly decreased.

The Results Indicate that essentially more cAMP is found in the duodenal juice after secretin stimulation than after CCK. cAMP in response to secretin seems to be mainly of pancreatic origin, that after CCK of hepatic origin. One of the first steps of stimulus-secretion coupling—the activation of the membrane bound adenylate cyclase system by secretin and CCK —seems to be intact in cystic fibrosis. The defect of this disease is probably beyond this mechanism.

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Abbreviations

cAMP:

cyclic 3′,5′-adenosine monophosphate

cGMP:

cyclic 3′,5′-guanosine monophosphate

CCK:

Cholecystokinin

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Authors and Affiliations

  1. Department of Pediatrics, University of Bonn, Adenauerallee 119, D-5300, Bonn, Federal Republic of Germany

    M. Becker & H. W. Rotthauwe

  2. Department of Pharmacology, University of Tübingen, Wilhelmstraße 56, D-7400, Tübingen, Federal Republic of Germany

    H. -J. Ruoff

Authors
  1. M. Becker
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  2. H. -J. Ruoff
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  3. H. W. Rotthauwe
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This study was supported by a grant from the Deutsche Forschungsgemeinschaft

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Becker, M., Ruoff, H.J. & Rotthauwe, H.W. Cyclic AMP in pancreatic and biliary secretion of children with chronic intrahepatic cholestasis and cystic fibrosis. Eur J Pediatr 134, 217–225 (1980). https://doi.org/10.1007/BF00441476

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  • DOI: https://doi.org/10.1007/BF00441476

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